Abstract | PURPOSE: PATIENTS AND METHODS: PIK3CA mutations in 504 tumor samples from participants in the neoadjuvant GeparQuattro, GeparQuinto, and GeparSixto studies were evaluated. All HER2-positive patients received either trastuzumab or lapatinib or the combination plus anthracycline- taxane chemotherapy. PIK3CA mutations were evaluated in formalin-fixed, paraffin-embedded tissues from core biopsies with a tumor cell content of ≥ 20% by using classical Sanger sequencing of exon 9 and exon 20. RESULTS: Overall, 21.4% of the patients harbored a PIK3CA mutation. Detection of a PIK3CA mutation was significantly associated with a lower pCR rate (19.4% with PIK3CA mutation v 32.8% with PIK3CA wild-type; odds ratio [OR], 0.49; 95% CI, 0.29 to 0.83; P = .008). In the 291 hormone receptor (HR) -positive tumors, pCR rate was 11.3% with a PIK3CA mutation compared with 27.5% with PIK3CA wild-type (OR, 0.34; 95% CI, 0.15 to 0.78; P = .011). In 213 patients with HR-negative tumors, pCR rate was 30.4% with PIK3CA mutation and 40.1% without (OR, 0.65; 95% CI, 0.32 to 1.32; P = .233; interaction test P = .292). In multivariable analysis, HR status and PIK3CA status provided independent predictive information. In patients with PIK3CA mutation, the pCR rates were 16%, 24.3%, and 17.4% with lapatinib, trastuzumab, and the combination, respectively (P = .654) and in the wild-type group, they were 18.2%, 33.%, and 37.1%, respectively (P = .017). Disease-free survival and overall survival were not statistically significantly different between patients with mutant and wild-type PIK3CA. CONCLUSION:
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Authors | Sibylle Loibl, Gunter von Minckwitz, Andreas Schneeweiss, Stefan Paepke, Annika Lehmann, Mahdi Rezai, Dirk M Zahm, Peter Sinn, Fariba Khandan, Holger Eidtmann, Karel Dohnal, Clemens Heinrichs, Jens Huober, Berit Pfitzner, Peter A Fasching, Fabrice Andre, Judith L Lindner, Christos Sotiriou, August Dykgers, Sanxing Guo, Stephan Gade, Valentina Nekljudova, Sherene Loi, Michael Untch, Carsten Denkert |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 32
Issue 29
Pg. 3212-20
(Oct 10 2014)
ISSN: 1527-7755 [Electronic] United States |
PMID | 25199759
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 by American Society of Clinical Oncology. |
Chemical References |
- Anthracyclines
- Antibodies, Monoclonal, Humanized
- Biomarkers, Tumor
- Quinazolines
- Taxoids
- Lapatinib
- Phosphatidylinositol 3-Kinases
- Class I Phosphatidylinositol 3-Kinases
- PIK3CA protein, human
- ERBB2 protein, human
- Receptor, ErbB-2
- Trastuzumab
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Topics |
- Adult
- Aged
- Anthracyclines
(administration & dosage)
- Antibodies, Monoclonal, Humanized
(administration & dosage)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Biomarkers, Tumor
(analysis)
- Breast Neoplasms
(drug therapy, genetics, pathology)
- Class I Phosphatidylinositol 3-Kinases
- Exons
- Female
- Genotype
- Humans
- Lapatinib
- Middle Aged
- Mutation
- Neoadjuvant Therapy
- Phosphatidylinositol 3-Kinases
(genetics)
- Quinazolines
(administration & dosage)
- Randomized Controlled Trials as Topic
- Receptor, ErbB-2
(antagonists & inhibitors, genetics)
- Taxoids
(administration & dosage)
- Trastuzumab
- Treatment Outcome
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